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Diurnal variations of plasma lipids, tissue and plasma lipoprotein lipase, and VLDL secretion rates in the rat. A model for studies of VLDL metabolism.

Circadian rhythms of plasma lipids and lipoproteins, lipoprotein lipase activities and VLDL secretion rates were studied in fed and food-deprived (12 h) male rats after a light/dark synchronization of 14 days. In ad libitum fed rats, a circadian rhythm of plasma triacylglycerol, blood glucose and liver glycogen was clearly identified. A rhythm was also identified for plasma cholesterol, but not phospholipids. The peak of plasma triacylglycerol occurred 2 h after the beginning of the light period (7.00 a.m.), and the nadir, 2 h after the beginning of the dark period (7.00 p.m.). The differences of plasma triacylglycerol at these two circadian stages were even more pronounced in food-deprived rats and were confined to the very-low-density lipoprotein (VLDL) fraction. Plasma post-heparin and heart and muscle lipoprotein lipase activities were 50-100% higher at 7.00 p.m., the time when plasma triacylglycerol were lowest, as compared to 7.00 a.m. Plasma post-heparin hepatic lipase and adipose tissue lipoprotein lipase activities, in contrast, did not change. VLDL secretion rates were somewhat higher at 7.00 a.m. compared to 7.00 p.m., but this difference was not significant. It is concluded that physiological variation of heart and muscle lipoprotein lipase together with small differences of VLDL secretion rates are responsible for normal range oscillations of plasma VLDL triacylglycerol levels.

Animals↗

Control of plasma arginine vasotocin in Kelp gulls (Larus dominicanus): roles of osmolality, volume, and plasma angiotensin II.

The physiological roles of plasma osmolality, volume, and angiotensin II (AII) in the control of plasma arginine vasotocin (AVT) have been evaluated in the Kelp gull. Plasma AVT (measured by radioimmunoassay) consistently followed the changes in plasma osmolality induced by dehydration, intravenous (iv) infusion of hypertonic saline, or iv infusion of hypotonic glucose solution. Osmoreceptor control of AVT was further characterized by the stimulatory effect of iv hypertonic mannitol but lack of effect of iv hypertonic urea. A direct volume effect on AVT release was demonstrated during hemorrhage, but blood volume reductions in excess of 10% were required. However, the volume of the extracellular fluid (ECF) compartment does have an important role in modulating the osmotic release of AVT in a way that enables contraction or expansion of ECF to be more expeditiously corrected than would occur if osmoreceptors alone regulated plasma AVT. Any physiological role of plasma AII in the control of plasma AVT is doubtful because after the iv infusion of AII for 60 min at 10, 25, 50, and 100 ng.min-1, only the two highest doses of AII, which produced supraphysiological plasma AII levels, caused elevations of plasma AVT. In addition, the osmotic reactivity of AVT release was not altered by exogenous administration of AII.

Angiotensin II↗

Correlations between free plasma estradiol and estrogens determined by bioluminescence in saliva, plasma, and urine during spontaneous and FSH stimulated cycles in women.

Estrone and estradiol (E1 + E2) concentrations in saliva were compared with four other parameters of estrogen status in five normal ovulatory women and ten FSH stimulated women selected for an in vitro fertilization program. E1 + E2 in saliva, plasma, and urine were assessed by a rapid, specific and sensitive enzymatic assay using bioluminescence. The free fraction of plasma estradiol was determined by equilibrium dialysis and total plasma estradiol by conventional radioimmunoassay. The pattern of E1 + E2 variation in saliva was similar to that of free plasma estradiol and the two parameters were correlated in both spontaneous and stimulated cycles. However, the lower correlation coefficient (r = 0.52, P less than 0.001) in spontaneous cycles compared with the high (r = 0.96, P less than 0.001) in the stimulated cycles shows that salivary E1 + E2 could be representative of plasma free estradiol in stimulated cycles but not in normal cycles. The free fraction of plasma estradiol reproduced the variation of total plasma estradiol in spontaneous as well as in FSH stimulated cycles and both parameters were strongly correlated (r = 0.91, P less than 0.001 and r = 0.90, P less than 0.001), respectively. The data show that salivary E1 + E2 concentrations are highly representative of the free fraction of E2 in plasma and at a lesser extend (r = 0.72, P less than 0.001) of total plasma E2 in FSH stimulated cycles.

Adult↗

Plasma renin activity and plasma prorenin are not suppressed in hypertensives surviving to old age.

An age related decline in plasma renin activity (PRA) has been described in normotensive and hypertensive subjects. Moreover, hypertensive patients are reported to have lower plasma prorenin levels. We therefore investigated whether that pattern of renin and prorenin suppression was apparent in white hypertensives and normotensives surviving to an older age. The study population consisted of 65 untreated hypertensives (office blood pressure > or = 160/95 mm Hg; mean age 79 +/- 6 SD; range 69 to 94 years) and 26 normotensives (mean age 77 +/- 8; range 66 to 99 years). The PRA in this population of older hypertensives (1.7 +/- 1.6 ng/mL/h) was not significantly different from normotensives of similar age (1.5 +/- 0.8 ng/mL/h). PRA was not correlated to age in either normotensives and hypertensives, but was inversely correlated to office blood pressure in the hypertensives (r = -0.25; P = .05). Plasma prorenin was also not significantly lower in older hypertensives (14.6 +/- 8.6 ng/mL/h) than in the normotensive controls (15.1 +/- 7.0 ng/mL/h). In normal subjects, but not in hypertensive patients, there was a positive relationship between plasma prorenin and age (r = 0.82; P < .001). However, elderly normotensive men had lower plasma prorenin levels (11.6 +/- 4.1 ng/mL/h) than normotensive women (18.6 +/- 7.4 ng/mL/h; P < .05). "Total renin" (PRA + plasma prorenin) was also lower in elderly normotensive men compared to women (13.2 +/- 3.9 ng/mL/h v 20.0 +/- 7.5 ng/mL/h; P < .05). In conclusion, neither PRA nor plasma prorenin are suppressed in normotensive or hypertensive subjects who survive to an old age. However, since an inverse relationship between PRA and age has been reported, it remains to be determined whether the renin/prorenin parameters were suppressed at any time or if normal renin and normal prorenin patients preferentially survive to an old age. The wide spectrum of plasma renin levels in the elderly indicates that treatment of these patients too can profitably be guided by pretreatment plasma renin levels.

Aged↗

Effects of perioperative parenteral glutamine-dipeptide supplementation on plasma endotoxin level, plasma endotoxin inactivation capacity and clinical outcome.

BACKGROUND & AIMS: We evaluated perioperative plasma endotoxin, plasma soluble CD14 molecule (sCD14), plasma endotoxin inactivation capacity (EIC) changes and clinical outcome after glutamine was provided in parenteral feedings to patients on whom gastrointestinal operations were performed using a prospective, randomized, double-blind study design. METHODS: Forty patients undergoing gastrointestinal operations were randomized into two groups, each had 20 patients. One group received standard parenteral nutrition and the other received the same formulation but supplemented with the dipeptide alanyl-glutamine, the two groups were isonitrogenous. The infusion was started from 1 day before operation to the 3rd day after operation for 5 days. Blood samples were collected on the morning of 1 day before operation, 3h after operation, and on the morning of 1, 4 and 7 days after operation and analyzed for plasma endotoxin level, plasma sCD14 level and EIC. RESULTS: There were no differences between the two groups on plasma endotoxin level. After surgery a rapid reduction in plasma EIC was observed in both groups, a significant restoration of the plasma EIC was observed on the morning of 1 and 4 days after surgery in the study group (0.12+/-0.02 and 0.078+/-0.022 EU/mL, respectively, P < 0.01). A significant rise in plasma sCD14 level was found in the study group on the morning of 1 and 4 days after surgery (14.32+/-1.69 and 10.34+/-1.14 microg/mL, respectively, P < 0.01). Shortened hospital stay was observed in the study group (11.7+/-2.0 days in the control group and 10.6+/-1.2 days on the study group respectively, P = 0.03). CONCLUSION: Perioperative parenteral nutrition supplemented with dipeptide alanyl-glutamine ameliorated postoperative immunodepression without direct effect on endotoxemia.

Adult↗

The relation between plasma cysteine, plasma homocysteine and coronary atherosclerosis.

Several studies have reported that elevated plasma levels of total homocysteine (tHcy) are related to an increased risk of cardiovascular disease. Only a few studies have looked at the effect of cysteine, another amino thiol, on cardiovascular disease risk. Therefore, in the present case-control study we compared plasma total cysteine (tCys) levels and plasma tHcy levels among subjects with severe coronary atherosclerosis (cases, n=131), subjects without severe coronary atherosclerosis (coronary controls, n=88) and healthy subjects (population-based controls, n=101). Cases were defined as those having > or =90% occlusion in one and > or =40% occlusion in a second coronary artery, while coronary controls had a maximum of 50% occlusion in only one coronary artery. Both males and females, aged 26--64 years were studied. We have previously reported that plasma tHcy is an independent risk factor for coronary atherosclerosis in this study population. In the present analysis, we found that cases had statistically significant higher mean plasma tCys levels than coronary controls and population-based controls (295.8+/-40.2, 279.0+/-35.5 and 282.6+/-32.4 micromol/l, respectively). The odds ratio (OR) of coronary atherosclerosis for the upper tertile of tCys compared with the bottom tertile was 2.5 (95% confidence interval (CI), 1.4--4.3). However, the association between tCys and coronary atherosclerosis was confounded to a great extent by risk factors (OR, 1.0; 95% CI, 0.5--2.0). The multivariate adjusted OR of coronary atherosclerosis per 1 S.D. increase in plasma tCys was 1.0 (95% CI, 0.8--1.3). The corresponding OR per 1 S.D. increase in plasma tHcy was 1.4 (95% CI, 1.1--1.8). We conclude that plasma tCys, unlike plasma tHcy, is not an independent risk factor for atherosclerosis.

Adult↗

The rise of the plasma lipid concentration elicited by dietary sodium chloride restriction in Wistar rats is due to an impairment of the plasma triacylglycerol removal rate.

Studies in humans have indicated that dietary salt restriction raises plasma levels of total cholesterol (TC) and triacylglycerols (TAG). In order to explain the mechanisms involved, a rat experimental model was developed consisting of chronic feeding ad libitum isocaloric diets with variable sodium chloride contents. Rates of synthesis of plasma TAG were measured either as the increase of plasma TAG after blocking its removal from plasma by the intra-arterial pulse infusion of Triton-WR 1339, or as the plasma rate of incorporation of [(14)C]-oleic acid [(14)C]-TAG. Plasma TAG removal rate was determined by the intra-arterial pulse infusion of a lipid emulsion. Severe salt restriction increased the plasma concentrations of TAG (71%) and of TC (10%). This result was not due to modification of the rate of synthesis of plasma TAG but was attributed to a 55% slower rate of removal of the TAG-containing lipoproteins. An increased plasma non-esterified fatty acid concentration, probably due to a salt restriction-related insulin resistance, may have impaired the activity of the enzyme lipoprotein lipase.

Animals↗

von Willebrand factor, fibrinogen and other plasma proteins as determinants of plasma viscosity.

Plasma viscosity and fibrinogen are risk factors for cardiovascular disease and on rheological grounds, it is widely believed that the latter is a major determinant of the former. However, other plasma constituents may also be important determinants of plasma viscosity. Our aim was to determine whether or not levels of von Willebrand factor contributed to plasma viscosity. We measured plasma viscosity, fibrinogen, von Willebrand factor, immunoglobulins G, A and M, total, HDL- and LDL-cholesterol, triglycerides and albumin in 95 patients with peripheral arterial disease and in 120 healthy controls. A stepwise multivariate analysis was performed to determine the major influences of plasma viscosity. We also measured fibrinogen, von Willebrand factor, immunoglobulins G, A and M, total, HDL- and LDL-cholesterol, triglycerides, albumin and viscosity in 32 smokers as they successfully progressed to being non-smokers. The level of von Willebrand factor was an independent influence on plasma viscosity in the controls (P < 0.05), patients (P < 0.01) and in the combined group (P < 0.001). von Willebrand factor, fibrinogen and plasma viscosity, but not the immunoglobulins, lipoproteins or albumin, fell (P < 0.05) in smokers as they became non-smokers. We find that von Willebrand factor contributes to plasma viscosity, hence a reduction in levels of von Willebrand factor should result in a reduction in viscosity. These data may have implications for the pathogenesis of cardiovascular disease.

Adult↗

1,25(OH)2D3 only affects long-term levels of plasma Ca2+ but not the rapid minute-to-minute plasma Ca2+ homeostasis in the rat.

Results from our lab have shown previously that parathyroid hormone (PTH) is not the key factor in the rapid regulation of plasma Ca2+. The possible role of 1,25(OH)2D3 in the rapid minute-to-minute regulation of plasma Ca2+, as addressed by a possible rapid non-genomic action of 1,25(OH)2D3, was therefore studied in vivo in rats. The rapid calcemic recovery from induction of hypocalcemia by a brief EGTA infusion was examined in vitamin D-depleted rats with intact parathyroid glands and in vitamin D depleted rats 1 h after parathyroidectomy (PTX). The influence of different levels of plasma 1,25(OH)2D3 on the rapid calcemic recovery from hypocalcemia was examined in PTX rats treated with 1,25(OH)2D3 for two days at two different doses of 0.2 microg/day, 0.05 microg/day or vehicle, and in PTX rats being BNX for two days, as well. Additionally, the long-term effect of 1,25(OH)2D3 on plasma Ca2+ homeostasis was examined. Plasma Ca2+ recovered significantly (P<0.05) 10 min after discontinuing EGTA in vitamin D-depleted rats with or without parathyroid glands. Plasma Ca2+ increased significantly (P<0.05) and at the same rate after induction of hypocalcemia in PTX rats with different levels of plasma 1,25(OH)2D3. The final levels of plasma Ca2+ obtained were set by 1,25(OH)2D3 in a dose-related manner. 1,25(OH)2D3 did not affect the rapid calcemic recovery from EGTA induced hypocalcemia, but only had an effect on the long-term plasma Ca2+ homeostasis in the rat.

Animals↗

Plasma lipoproteins and the synthesis and turnover of plasma triglyceride in normal and genetically obese mice.

1. Lipoproteins in the plasma of mice were characterized by agarose-gel chromatography and polyacrylamide-gel electrophoresis: genetically obese (ob/ob) mice exhibited hyperlipoproteinaemia (compared with lean mice), largely owing to an increase in the concentration of cholesterol in high-density lipoprotein. Plasma concentrations of triglyceride and phospholipid were not markedly increased in genetically obese mice. 2. The formation of glycerolipids in liver and plasma was investigated with (14)C-labelled precursors. The synthesis of hepatic triglyceride and phospholipid from glucose or palmitate was enhanced in ob/ob mice, compared with lean mice. The rate of entry of triglyceride into plasma, calculated from the time-course of incorporation of (14)C from [(14)C]palmitate into plasma triglyceride, was increased in ob/ob mice (0.5mumol of fatty acid/min, compared with 0.2 in lean mice). 3. The removal from plasma of murine lipoprotein triglyceride-[(14)C]fatty acid was increased in ob/ob mice (half-time 2.2min, compared with 7.2min in lean mice). Similar results were obtained with an injected lipid emulsion (Intralipid). 4. From these measurements, estimates of the rates of turnover of plasma triglyceride in mice (fed on a mixed diet, female, 3 months old) are about 1.0mumol of fatty acid/min in ob/ob mice, and 0.25 in lean mice. 5. The major precursor of hepatic and plasma triglyceride in lean and ob/ob mice was calculated to be plasma free fatty acid. 6. These results are discussed, in connexion with the role of the liver in triglyceride metabolism in mice, especially in relation to genetic obesity.

Animals↗

Activation of inactive plasma renin by plasma and tissue kallikreins.

1. Normal human plasma contains a proactivator of inactive renin. The pro-activator is activated at physiological pH in plasma that has been pretreated with acid. This activation in vitro leads to the conversion of inactive renin into the active form with simultaneous generation of kallikrein activity. 2. The endogenous activator of inactive renin has the same pH profile and inhibitor spectrum as plasma kallikrein. 3. Inactive renin can also be activated by exposure of plasma to exogenous trypsin, and in normal plasma the quantities of inactive renin that are activated after acidification and with trypsin are identical. Prekallikrein (Fletcher factor)-deficient plasma, however, has much lower renin activity after acidification than with trypsin. Thus acid activation of inactive renin depends on plasma prekallikrein, whereas the action of trypsin is independent of prekallikrein. 4. Highly purified tissue (pancreatic) kallikrein, in a concentration of less than 2 X 10(-8) mol/l, activates inactive renin that has been isolated from plasma by ion-exchange chromatography. In this respect it is at least 100 times more potent than trypsin. 5. It is therefore possible that plasma and/or tissue (renal) kallikreins are also involved in the activation of inactive renin in vivo.

Enzyme Activation↗

Human plasma vitamin E kinetics demonstrate rapid recycling of plasma RRR-alpha-tocopherol.

A kinetic model of vitamin E transport in humans is described using data from our studies with deuterium-labeled stereoisomers of alpha-tocopherol (RRR- and SRR-). In normal subjects, both alpha-tocopherols are present at similar concentrations in chylomicrons, but by 24 hr, RRR-alpha-tocopherol is at higher plasma concentrations because RRR-alpha-tocopherol is preferentially incorporated into very low density lipoproteins, which are then secreted into plasma. In three nondiscriminator patients with familial isolated vitamin E deficiency, the fractional disappearance rates (mean +/- SD) of deuterium-labeled RRR- and SRR-alpha-tocopherols in plasma were 1.4 +/- 0.6 and 1.3 +/- 0.3 pools per day, respectively (difference, 0.1 +/- 0.3). In these patients, plasma concentrations of both RRR- and SRR-alpha-tocopherols decreased similarly to SRR-alpha-tocopherol in controls. In six controls, fractional disappearance rates of deuterium-labeled RRR-alpha-tocopherol (0.4 +/- 0.1 pool per day) were significantly (P < 0.01) slower than for SRR- (1.2 +/- 0.6). The differences (0.8 +/- 0.6 pool per day) between these two rates in controls estimate the rate at which RRR-alpha-tocopherol, which had left the plasma, was returned to the plasma. Although plasma labeled RRR-alpha-tocopherol concentrations in controls appear to change slowly, these data show that both RRR- and SRR-alpha-tocopherols leave the plasma rapidly, but only RRR-alpha-tocopherol is returned to the plasma, likely in nascent very low density lipoproteins. This recycling of RRR-alpha-tocopherol accounts for nearly 1 pool of alpha-tocopherol per day.

Administration, Oral↗

Removal of IgG from normal plasma and plasma from untreated patients with active Crohn's disease--effect on levels of contact factors.

Protein G columns were used to remove IgG from human plasma, and the effect on levels of factor XII, factor XI and prekallikrein was studied in functional tests. IgG was detected in PAGE immunoblot experiments with Fc-specific antibodies. Removal of the bulk of IgG in a procedure based on a low plasma dilution (1+2.5) allowed the passage of an IgG fraction along with the contact factors. This fraction was found to be present in higher amounts in plasma from patients with Crohn's disease (n=5) than in control plasma (n=12). In a previous study, PAGE immunoblot experiments showed that part of the prekallikrein was removed along with IgG when a higher plasma dilution (1+10.8) was used (Scand J Clin Lab Invest 1999; 59: 55-64). This observation was supported by results in the present work based on parallel assays with the peptide substrates S-2302 and Bz-Pro-Phe-Arg-pNA. The prekallikrein fraction removed was present in a functional state differing from the main part of prekallikrein by yielding kallikrein with a significantly increased activity against the substrate S-2366. This prekallikrein fraction was present in higher amounts in patient plasma than in control plasma. Part of the corresponding amidase activity was blocked by lima bean trypsin inhibitor, suggesting its presence in association with factor XI. The results also indicated that prekallikrein activator activity was connected with this fraction. With the high dilution procedure an extensive removal of IgG from the patient plasma was obtained compared to the control plasma.

Adult↗

The effects of competitive displacement on haloperidol's plasma distribution in normolipidemic and hyperlipidemic plasma.

PURPOSE: To assess whether dyslipidemia affects haloperidol's overall plasma distribution when it is in the presence of another highly protein bound drug that competes for plasma protein binding sites. METHODS: We performed in vitro studies in which warfarin sodium was pre-incubated in normolipidemic and hyperlipidemic plasma samples in varying concentrations. Following the pre-incubation with warfarin, [3H]-haloperidol mixed with unlabeled haloperidol was added to the plasma samples. The plasma was separated into its lipoprotein and lipoprotein deficient fractions by density gradient ultracentrifugation and haloperidol distribution was determined. RESULTS: Our results indicate that when normolipidemic plasma was pre-incubated with various concentrations of warfarin no significant redistribution of haloperidol was noted among the various plasma lipoprotein fractions. However, in the case of the hyperlipidemic plasma, pre-incubating with warfarin did result in a significant redistribution of haloperidol from the lipoprotein-deficient fraction to the very-low-density and low-density fractions of lipoproteins. CONCLUSION: Understanding how plasma lipoproteins influence competitive displacement interactions would be valuable in helping to explain and perhaps predict pharmacokinetic parameters that may affect clinical outcome. The clinical significance of competitive displacement of drugs in patients with dyslipidemia requires further study.

Anticoagulants↗

Human plasma alpha 2-macroglobulin. An inhibitor of plasma kallikrein.

Activation of plasma kallikrein arginine esterase activity by kaolin resulted in peak activity at 1 min of incubation and a 50% reduction in activity at 5 min in normal plasma, and 30% reduction in the plasma of patients with hereditary angioneurotic edema who lacked the C1 inactivator. The peak esterolytic activity was inhibited by soybean trypsin inhibitor whereas the 5 min activity was resistant to this inhibitor. Acid treatment of normal and hereditary angioneurotic edema plasma destroyed the factor responsible for the fall in esterase activity at 5 min and the factor which rendered the esterase resistant to soybean trypsin inhibitor. Purified alpha(2)-macroglobulin inhibited approximately 50% of the TAMe esterase activity of purified plasma kallikrein without changing its activity toward basic amino acid esters. The interaction between the alpha(2)-macroglobulin and kallikrein resulted in alterations in the gel filtration chromatographic pattern of the TAMe esterase and biologic activity of kallikrein, indicating that kallikrein was bound to the alpha(2)-macroglobulin. The TAMe esterase activity of this complex, isolated by column chromatography, was resistant to C1 inactivator and SBTI. Studies of incubation mixtures of kallikrein, alpha(2)-macroglobulin and C1 inactivator suggested that these inhibitors compete for the enzyme, and that the alpha(2)-macroglobulin partially protects the esterase activity of kallikrein from C1 inactivator. The alpha(2)-macroglobulin isolated from kaolin-activated plasma possessed 240 times the esterolytic activity of the alpha(2)-macroglobulin purified from plasma treated with inhibitors of kallikrein and of its activation. The alpha(2)-macroglobulin blocked the uterine-containing activity and vascular permeability-inducing effects of plasma kallikrein. These studies suggest that the alpha(2)-macroglobulin is a major plasma inhibitor of kallikrein and provide a new example of an interrelationship between the coagulation, fibrinolytic, and kallikrein enzyme systems.

Alpha-Globulins↗

Postprandial changes in plasma and serum viscosity and plasma lipids and lipoproteins after an acute test meal.

The influence of a fat-rich test meal on postprandial changes in plasma viscosity and serum viscosity was assessed in 12 normolipidemic adults. After a 12-14-h fast, volunteers (five men and seven women aged 23-50 y) were challenged with a test milk shake containing 50 g fat/m2 body surface area (BSA). Plasma viscosity, serum viscosity, and plasma lipids and lipoproteins were assessed at 0, 2, 3, 4, and 6 h. Viscosity values were determined by using a Mettler Contraves LS-40 rotational microviscometer. Postprandial changes in the study variables were assessed by area under the curve and included triacylglycerols (2.02 mmol/L), plasma viscosity (-0.10 mPa.s), and serum viscosity (-0.01 mPa.s). Peak plasma triacylglycerol concentrations were significantly greater than those observed at baseline (P = 0.0022). There were no significant changes in any other variable when fasting and peak values were compared. Peak plasma viscosity increased in three and decreased in two subjects with no changes in the remaining seven subjects. Changes in peak plasma viscosity ranged from -7% to 7% with similar changes for serum viscosity, from -8% to 10%, and a slightly greater range for plasma fibrinogen, -16% to 10%. In this cohort of normotriacylglycerolemic subjects, there were no significant postprandial changes in plasma viscosity or serum viscosity.

Adult↗

Plasma choline and betaine and their relation to plasma homocysteine in normal pregnancy.

BACKGROUND: Plasma concentrations of total homocysteine (tHcy) decrease during pregnancy. This reduction has been investigated in relation to folate status, but no study has addressed the possible role of betaine and its precursor choline. OBJECTIVE: We investigated the courses of plasma choline and betaine during normal human pregnancy and their relations to plasma tHcy. DESIGN: Blood samples were obtained monthly; the initial samples were taken at gestational week (GW) 9, and the last samples were taken approximately 3 mo postpartum. The study population comprised 50 women of West African descent. Most of the subjects took folic acid irregularly. RESULTS: Plasma choline (geometric x; 95% reference interval) increased continuously during pregnancy, from 6.6 (4.5, 9.7) micromol/L at GW 9 to 10.8 (7.4, 15.6) micromol/L at GW 36. Plasma betaine decreased in the first half of pregnancy, from 16.3 (8.6, 30.8) micromol/L at GW 9 to 10.3 (6.6, 16.2) micromol/L at GW 20 and remained constant thereafter. We confirmed a reduction in plasma tHcy, and the lowest concentration was found in the second trimester. From GW 16 onward, an inverse relation between plasma tHcy and betaine was observed. Multiple regression analysis showed that plasma betaine was a strong predictor of plasma tHcy from GW 20 onward. CONCLUSIONS: The steady increase in choline throughout gestation may ensure choline availability for placental transfer with subsequent use by the growing fetus. Betaine becomes a strong predictor of tHcy during the course of pregnancy. Both of these findings emphasize the importance of choline and betaine status during normal human pregnancy.

Adult↗

Epicatechin in human plasma: in vivo determination and effect of chocolate consumption on plasma oxidation status.

Diets that are rich in plant foods have been associated with a decreased risk for specific disease processes and certain chronic diseases. In addition to essential macronutrients and micronutrients, the flavonoids in a variety of plant foods may have health-enhancing properties. Chocolate is a food that is known to be rich in the flavan-3-ol epicatechin and procyanidin oligomers. However, the bioavailability and the biological effects of the chocolate flavonoids are poorly understood. To begin to address these issues, we developed a method based on HPLC coupled with electrochemical (coulometric) detection to determine the physiological levels of epicatechin, catechin and epicatechin dimers. This method allows for the determination of 20 pg (69 fmol) of epicatechin, which translates to plasma concentrations as low as 1 nmol/L. We next evaluated the absorption of epicatechin, from an 80-g semisweet chocolate (procyanidin-rich chocolate) bolus. By 2 h after ingestion, there was a 12-fold increase in plasma epicatechin, from 22 to 257 nmol/L (P < 0.01). Consistent with the antioxidant properties of epicatechin, within the same 2-h period, there was a significant increase of 31% in plasma total antioxidant capacity (P < 0.04) and a decrease of 40% in plasma 2-thiobarbituric acid reactive substances (P < 0.01). Plasma epicatechin and plasma antioxidant capacity approached baseline values by 6 h after ingestion. These results show that it is possible to determine basal levels of epicatechin in plasma. The data support the concept that the consumption of chocolate can result in significant increases in plasma epicatechin concentrations and decreases in plasma baseline oxidation products.

Adult↗